Echinococcus granulosus sensu stricto and antigen B may decrease inflammatory bowel disease through regulation of M1/2 polarization.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic idiopathic disease characterized by inflammation-related epithelial barrier damage in the intestinal tract. Helminth infection reduces autoimmune disease symptoms through regulation of inflammatory responses based on hygiene theory. However, the underlying mechanisms remain unclear. METHODS: BALB/c mice were infected with microcysts of E. granulosus sensu stricto and drank water containing 3.5% dextran sodium sulfate (DSS) at the 100th day post-infection. After 7 days of drinking DSS, the mouse body weight change and disease activity index (DAI) were recorded every day, and colon length and histological score were evaluated after sacrifice. After injection with antigen B (AgB), inducible nitric oxide synthase (iNOS) and Fizz1 expression and F4/80+CD11c+ M1 and F4/80+CD206+ M2 in the peritoneal cells and colon tissues were analysed by qPCR and flow cytometry, respectively. Gut microbiota were profiled by 16S rRNA sequencing of the mouse faecal samples. For in vitro assay, RAW264.7 macrophages were cultured in medium containing AgB before induction by lipopolysaccharide (LPS). Then, NO in the supernatant was measured, and the expression of cytokine genes associated with macrophages were determined by qRT-PCR. RESULTS: Echinococcus granulosus s.s. infection and AgB significantly reduced the symptoms and histological scores of IBD induced by DSS (P < 0.05). Flow cytometry showed that AgB inoculation increased F4/80+ and CD206+ in peritoneal cells. The results of qPCR showed that AgB significantly decreased iNOS and increased Fizz1 expression in the colon of mice inoculated by DSS (P < 0.05). Furthermore, AgB injection led to significant changes in the profiles of five genera (Paraprevotella, Odoribacter, Clostridium cluster XlVa, Oscillibacter, and Flavonifractor) in faecal samples. In vitro analysis showed that AgB reduced NO levels (P < 0.01), with a significant decrease in iNOS expression (P < 0.05) in RAW264.7 cells induced by LPS. CONCLUSIONS: Echinococcus granulosus infection and AgB may improve IBD conditions by inducing an M2-predominant cellular (F4/80+ CD206+) profile and decreasing type 1 macrophages (F4/80+CD11c+) in the intestinal lamina propria. In addition, AgB intervention induced changes in the microbiota condition of the gastrointestinal duct and reversed NO expression. Thus, AgB may be a drug candidate for IBD treatment.

High endemicity of alveolar echinococcosis in Yili Prefecture, Xinjiang Autonomous Region, the People's Republic of China: Infection status in different ethnic communities and in small mammals.

Alveolar echinococcosis (AE) is a life-threatening disease in humans caused by the larval stage of Echinococcus multilocularis. The tapeworm is transmitted between small mammals and dogs/foxes in the Northern Hemisphere. In this study 286 AE cases were reported from eight counties and one city in Yili Prefecture, Xinjiang Autonomous Region, the People's Republic of China from 1989 to 2015 with an annual incidence (AI) of 0.41/100,000. Among the patients, 73.08% were diagnosed in the last 11 years. Four counties in the high mountainous areas showed higher AI (0.51-1.22 cases/100,000 residents) than the four counties in low level areas (0.19-0.29/100,000 residents). The AI of AE in Mongolian (2.06/100,000 residents) and Kazak (0.93/100,000 residents) ethnic groups was higher than the incidence in other ethnic groups indicating sheep-farming is a risk for infection given this activity is mainly practiced by these two groups in the prefecture. A total of 1411 small mammals were captured with 9.14% infected with E. multilocularis metacestodes. Microtus obscurus was the dominant species in the mountain pasture areas with 15.01% of the voles infected, whereas Mus musculus and Apodemus sylvaticus were the dominant small mammals in the low altitude areas. Only 0.40% of A. sylvaticus were infected with E. multilocularis. PCR amplification and sequencing analysis of the mitochondrial cox1 gene showed that E. multilocularis DNA sequences from the small mammals were identical to isolates of local human AE cases. The overall results show that Yili Prefecture is a highly endemic area for AE and that the high-altitude pasture areas favorable for M. obscurus may play an important role in its transmission in this region.

Molecular evidence of Tula virus in Microtus obscurus in the region of Yili, Xinjiang, China.

BACKGROUND: Hantaviruses are important zoonotic pathogens, and they pose a profound risk to public health. So far, there has been no evidence showing that Tula virus (TULV), one species of hantavirus, is endemic in China. In this study, we captured rodents and found that the Tula virus had infected voles in Yili region, Xinjiang, China. METHODS: Rodents were captured by flooding their burrows in mountain pasture areas in Narati, Xinyuan County, Xinjiang, China. Hantavirus L gene fragments were amplified by nest RT-PCR using genus-specific primers. Positive samples were further identified by sequencing of RT-PCR products of S gene fragment for species identification. To identify the species of captured small mammals, the rodents' cytochrome b (Cytb) was amplified by PCR and sequenced. Phylogenetic analysis was used to show the clustering and evolution relationship of the viral nucleic acids. RESULTS: Here, 31 out of 198 voles captured (16%) were infected with TULV. Host sequencing analysis showed these voles were Microtus obscurus (M. obscurs). Alignment and phylogenetic analysis of the exon region (1191 bp) of the hantavirus S gene confirmed that all of the detected amplicons were TULV, which was similar to one strain of TULV identified in Kazakhstan. CONCLUSION: This is the first identification of Tula virus in China, and we found that M. obscurus acts as a natural reservoir for carrying the virus. Although the infection rate in the local human population remains unknown, the high prevalence of TULV in the small mammals in the region constitutes a risk that this putative pathogen may spread to the local population.

Echinococcus granulosus Infection Results in an Increase in Eisenbergiella and Parabacteroides Genera in the Gut of Mice.

Cystic echinococcosis (CE) is a chronic infectious disease caused by Echinococcus granulosus. To confirm whether the infection impacts on the gut microbiota, we established a mouse model of E. granulosus infection in this study whereby BALB/c mice were infected with micro-cysts of E. granulosus. After 4 months of infection, fecal samples were collected for high-throughput sequencing of the hypervariable regions of the 16S rRNA gene. Sequence analysis revealed a total of 13,353 operational taxonomic units (OTUs) with only 40.6% of the OTUs having genera reference information and 101 of the OTUs were significantly increased in infected mice. Bioinformatics analysis showed that the common core microbiota were not significantly changed at family level. However, two genera (Eisenbergiella and Parabacteroides) were enriched in the infected mice (P AMOV A < 0.05) at genus level. Functional analysis indicated that seven pathways were altered in the E. granulosus Infection Group compared with the Uninfected Group. Spearman correlation analysis showed strong correlations of IgG, IgG1 and IgG2a with nine major genera. E. granulosus cyst infection may change the gut microbiota which may be associated with metabolic pathways.

Assessment and prognostic analysis of EGFR mutations or/and HER2 overexpression in Uygur's Non-small Cell Lung Cancer.

AIM: The epidermal growth factor receptor (EGFR) mutations and human epidermal growth factor receptor HER-2/neu (HER2) have been established roles in the signal transduction pathways leading to cell growth and differentiation. The present study focus on the significance of EGFR mutations combined with HER2 overexpression on survival outcomes in Non-small Cell Lung Cancer patients in Uygur population. METHODS: A total of 111 consecutive Uygurods: A total of 111 consecutive Cell Lung Cancer under went lung Cell Lung biopsy or surgery at the Affiliated Tumor Hospital of Xin Jiang Medical University between March 2009 and January 2013 were included in this retrospective study. All the patients included had received gefitinib 250 mg once daily. The HER2 expression were evaluated by immunohistochemical staining with score of membranous staining being 0 = none, 1 = weak, 2 = 10-30% cells, 3≥30% cells stained, and Real-time PCR techniques were conducted to detect mutations of EGFR through 21 kinds of human EGFR gene mutation detection kits. A retrospective review of the medical records was analyzed to determine the correlation between the presence of EGFR mutations combined with HER2 overexpression and clinicopathological factors. RESULTS: The overall rate of EGFR mutation was 10.81% (n = 12), which mainly involved exons 19 (83.33%, n = 10), 21 (16.67%, n = 2). The overall rate of HER2 overexpression was 21.62% (n = 24). EGFR mutation combined with HER2 overexpression analysis was performed in 111 patients, with an overall rate of 5.41% (n = 6). Median progression-free survival and overall survival were significantly longer in the EGFR mutations group than in the wild type group (PFS: 10.0±1.5 versus 3.8±1.4 months, P = 0.000; OS: 27.3±2.9 versus 19.1±4.7 months, P = 0.000). The ORR in patients with HER2 overexpression was 29.17%, and 13.80% in those patients with HER2 negative, but no significant difference (P = 0.121). The median PFS and OS in HER2 positive group showed no significant difference compared with HER2 negative group (PFS: 4.7±1.2 months versus 3.9±1.6 months, P = 0.085; OS: 20.5±2.4 versus 19.2±2.6 months, P = 0.094). As regarding to ORR, PFS and OS, EGFR mutations combined with HER2 overexpression patients showed no superior efficacy to gefitinib treatment compared with EGFR mutations combined with HER2 negative. CONCLUSION: In Uygur population, progression-free survivals were improved in Non-small Cell Lung Cancer with EGFR mutations. HER2 overexpression provided a poor prognostic factor in Non-small Cell Lung Cancer.

Intracranial transplant of olfactory ensheathing cells can protect both upper and lower motor neurons in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal disease that involves the degeneration of cortical and spinal motor neurons. Mutant SOD1(G93A) rats constitute a good animal model for this pathological condition. We have previously demonstrated that transplantation of neonatal olfactory ensheathing cells (OECs) into the dorsal funiculus of the spinal cord of mutant SOD1(G93A) transgenic rats increases the survival of spinal motor neurons and remyelinates the impaired axons through the pyramidal tract. In the present study, we examine whether intracranial cell implantation could also exert a similar effect on cortical motor neurons and on the lower motor neurons in the spinal cord. We injected OECs from the bulb of 7-day-old GFP green rats into the corona radiata of adult SOD1 mutant rats stereotaxically to observe any changes of the upper motor neurons as well as the lower motor neurons. We found that more motor neurons at both the motor cortices and ventral horns of the spinal cord survived in grafted ALS rats than in control rats. Prolonged survival and behavioral tests including a screen test, hind limb extension, rotarod, and gait control showed that the treated animals were better than the control group. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Olfactory ensheathing cell transplantation into spinal cord prolongs the survival of mutant SOD1(G93A) ALS rats through neuroprotection and remyelination.

Amyotrophic lateral sclerosis (ALS) is a progressively fatal, incurable, neurodegenerative disorder. In this study, we investigated whether olfactory ensheathing cells (OEC) transplantation could provide protection to motor neurons and enable remyelination in mutant SOD1(G93A) transgenic rats with ALS. Seventy-two rats were divided into four groups: SOD1(G93A) rats (n = 20); medium+SOD1(G93A) rats (n = 20); OECs+SOD1(G93A) rats (n = 24); and another eight wild-type rats were used as controls. About 5 µL (1 × 10(5)) OECs in DF12 medium was injected into the dorsal funiculus of the thoracic spinal cord at a predetermined depth. Survival analysis revealed a significant increase in the survival time in OEC+SOD1(G93A) rats. Body weight records and inclined board test showed a significant difference between OEC+SOD1(G93A) and SOD1(G93A) from the onset at 7 days to 11 days (P < 0.05). Four weeks following transplantation, motor neuron counts in the ventral horn of the spinal cord noted a significant motor neuron loss in SOD1(G93A) rats when compared with wild-type rats (P < 0.001), and much less neuronal loss and collapse was noted in OEC+SOD1(G93A) rats when compared with SOD1(G93A) rats(P < 0.001); immunohistochemistry and Western blot analysis of choline acetyltransferase supported the motor neuron count. Images of confocal microscope indicated that the transplanted OECs had survived for more than 4 weeks and migrated 4.2 mm through the spinal cord. Evidence of remyelination of transplanted OEC was captured with triple fluorescence labeling of green fluorescent protein, neurofilament, and myelin basic protein and was further confirmed by Western blot analysis of MPB. In conclusion, the transplanted OECs could serve as a source of neuroprotection and remyelination to modify the ALS microenvironment.